12-10125968-C-T

Position:

• chr12-10125968-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_197947.3(CLEC7A):​c.341-520G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,170 control chromosomes in the GnomAD database, including 49,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (49046 hom., cov: 33)
• Consequence: CLEC7A NM_197947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

Genes affected

CLEC7A (HGNC:14558): (C-type lectin domain containing 7A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

CLEC7A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC7A	NM_197947.3	c.341-520G>A		intron_variant		ENST00000304084.13	NP_922938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC7A	ENST00000304084.13	c.341-520G>A		intron_variant		1	NM_197947.3	ENSP00000302569.8

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120638 AN: 152054 Hom.: 49014 Cov.: 33

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.804

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.793 AC: 120714 AN: 152170 Hom.: 49046 Cov.: 33 AF XY: 0.784 AC XY: 58307 AN XY: 74384

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.852

Gnomad4 OTH AF: 0.794

Alfa AF: 0.808 Hom.: 7919

Bravo AF: 0.785

Asia WGS AF: 0.411 AC: 1428 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4763446; hg19: chr12-10278567;